title: A novel DNA vaccine technology conveying protection against a lethal herpes simplex viral challenge in mice.
abstract: While there are a number of licensed veterinary DNA vaccines, to date, none have been licensed for use in humans. Here, we demonstrate that a novel technology designed to enhance the immunogenicity of DNA vaccines protects against lethal herpes simplex virus 2 (HSV-2) challenge in a murine model. Polynucleotides were modified by use of a codon optimization algorithm designed to enhance immune responses, and the addition of an ubiquitin-encoding sequence to target the antigen to the proteasome for processing and to enhance cytotoxic T cell responses. We show that a mixture of these codon-optimized ubiquitinated and non-ubiquitinated constructs encoding the same viral envelope protein, glycoprotein D, induced both B and T cell responses, and could protect against lethal viral challenge and reduce ganglionic latency. The optimized vaccines, subcloned into a vector suitable for use in humans, also provided a high level of protection against the establishment of ganglionic latency, an important correlate of HSV reactivation and candidate endpoint for vaccines to proceed to clinical trials.
authors.affiliation: Coridon Pty Ltd, Brisbane, Queensland, Australia.
authors.forename: Julie L
authors.initials: JL
authors.lastname: Dutton
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.forename: Wai-Ping
authors.initials: WP
authors.lastname: Woo
authors.forename: Joshua O
authors.initials: JO
authors.lastname: Marshak
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.forename: Meei-li
authors.initials: ML
authors.lastname: Huang
authors.forename: Lichun
authors.initials: L
authors.lastname: Dong
authors.forename: Ian H
authors.initials: IH
authors.lastname: Frazer
authors.forename: David M
authors.initials: DM
authors.lastname: Koelle
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D003062:Codon; D005260:Female; D006561:Herpes Simplex / Q000276:immunology* / Q000401:mortality / Q000517:prevention & control*; D018258:Herpesvirus 2, Human / Q000235:genetics / Q000276:immunology*; D051379:Mice; D016176:T-Lymphocyte Subsets / Q000276:immunology; D054875:Ubiquitination; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D003062:Codon; D019444:Vaccines, DNA; D014759:Viral Envelope Proteins; D014765:Viral Vaccines